The Microbiota in Health and Disease

Question 1

What is the likely cause of inflammation in IBD?

Answer 1

Dysregulated host immune response to the gut microbiota

Question 2

Describe the role of microbe in the development in IBD

Answer 2

Increased mucosal bacterial load is present

Show reduced bacterial diversity (In IBD, but in IBS there is an altered diversity)

Broad spectrum antibiotics can have some efficacy in reducing symptoms

IBD does not occur in germ free animals

Reduced temporal stability in microbiota composition

Question 3

Why is it hard to disentangle cause and effect when assessing IBD microbiota?

Answer 3

Many features of IBD itself could affect the microbiota

Question 4

What features of IBD could affect the microbiota?

Answer 4

• Antibiotic use (•Reduced bacterial diversity and increases in Enterobacteriaceae can occur as a result of broad-spectrum antibiotic use)
• Inflammation (•causes reduced bacterial diversity and an increase in enterobacteriaceae)
• Diarrhoea
• Host diet
• Host genotype

Question 5

What diseases are associated with changes in the gut microbiota?

Answer 5

IBS

IBD

Colorectal cancer (Fusobacterium, E.Coli)

Diabetes (includes opportunist pathogens)

CDAD - lack of diversity

Question 6

Is there a difference in gut microbiota in inflamed vs non-inflamed tissue?

Answer 6

No

Question 7

What is the microbiota in Chron’s disease like?

Answer 7

Enterobacteriaceae appeared to be slightly elevated in Crohn’s disease patients

Question 8

What are probiotics?

Answer 8

Probiotics are live microorganisms which, when administered in adequate amounts confer a health benefit on the host

Question 9

What are prebiotics?

Answer 9

A fermented food or ingredient that affects the activity / composition of the gut microbiota and cause a resultant health benefit to the host. (food for resident bacteria)

Question 10

Give examples of Pre biotics

Answer 10

FOS, Inulin, GOS, Lactulose

Natural sources include garlic leeks and onion

Question 11

Give examples of health benefits associated with prebiotics

Answer 11

Improves calcium uptake

Can increase stool frequency which reduces the risk of colon cancer (Native chicory inulin)

Question 12

What is the mechanism of action for probiotics?

Answer 12

1. Competition
2. Bioconversions (diet)
3. Production of vitamins
4. Direct antagonism (pathogens)
5. Competitive exclusion
6. Barrier function
7. Reduce inflammation
8. Immune stimulation

Question 13

What is the effect of probiotics on the prevention of GI diseases?

Answer 13

Beneficial in treatment and prevention of GI diseases

Question 14

Which diseases do probiotics have a therapeutic effect on?

Answer 14

CDAD, antibiotic associated diarrhoea, helicobacter pylori, IBS

Question 15

How do you combat a reduction in faecalibacterium prausnitzii?

Answer 15

Provide specific prebiotics designed to boost numbers of F. prausnitzii

Design F. prau as a biotherapeutic agent (medical probiotic)

Question 16

How do you combat an increase in enterobacteriaceae?

Answer 16

Reduce antibiotic use to prevent decline in commensals

Include more dietary fibre in diet to boost bacterial diversity

Question 17

What is the effect of a FODMAP diet? Used to treat IBS

(fermentable oligosaccharides, disaccharides, monosaccharides and polyols)

Answer 17

Diet designed to reduce bacterial fermentation; identifies key foods to exclude permanently

Question 18

What is the effect of prebiotics?

Answer 18

Improved gut function

Management of inflammatory bowel disease, reduction in inflammatory markers

Prebiotics increase gut transit and therefore reduce the risk of colon cancer (reduced DNA damage and cell proliferation, faster gut transit)

Prebiotics (FOS/Inulin) increase calcium absorption and bone health

Consumption of prebiotics instead of sugars can lower glycaemic index (consumption of foods containing non-digestible carbohydrates instead of sugars induces a lower blood glucose rise after meals compared to those containing sugars)

Question 19

What are the effects of antibiotics on the gut microbiota?

Answer 19

Most antibiotics are broad-spectrum antibiotics - active against target pathogen but also ‘kill’ commensal bacteria

There is a loss of diversity and there exists opportunity for pathogen colonisation – example – clostridium difficile - expands to occupy empty niches following antibiotic therapy.

Question 20

What is the effect of overgrowth of C. Diff?

Answer 20

Results in toxin production, abdominal pain, fever (CDAD)

c diff associated diarrhoea

C diff spores are resistant to antibiotics

Question 21

What is the effect of C diff strains that are antibiotic resistant?

Answer 21

Recurring C diff infections

Question 22

What is FMT?

Answer 22

Faecal microbial transplantation

Sample from screened healthy volunteer donor transplanted into recipient (enema, colonoscopy, naso-enteric tube, capsules)

Donor microbiota repopulates large intestine, displaces c diff, prevents reinfection

Question 23

Are there any clear cut contraindications for the application of fecal material transplantation?

Answer 23

NO

Question 24

Take Home messages

Answer 24

Changes in gut microbiota composition may be associated with diseases - this does not always mean they CAUSE the disease

Antibiotics kill pathogenic bacteria causing disease AND kill many of the commensal, resident bacteria that may be important for health

Clostridium difficile can over-grow and cause disease following antibiotic therapy

The most effective treatment for recurring CDAD is properly provided FMT

Probiotics are added live bacteria that can be used to treat the symptoms of some disease

but different probiotics have different activities –

make sure the required activity has been scientifically proven with that specific probiotic

Prebiotics are a dietary food for the resident gut microbiota

– and can boost numbers of beneficial bacteria that use them for growth